Limits...
Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats.

Lee JC, Cha CI, Kim DS, Choe SY - J Pathol Transl Med (2015)

Bottom Line: Compared with the control unconditioned media, CM infusion reduced the ventricular pressure, the right ventricle/(left ventricle+interventricular septum) ratio, and maintained respiratory function in the treated animals.Also, the number of interleukin 1α (IL-1α), chemokine (C-C motif) ligand 5 (CCL5), and tissue inhibitor of metalloproteinase 1 (TIMP-1)-positive cells increased in lung samples and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL)-positive cells decreased significantly in the CM treated animals.From our in vivo data in the rat model, the observed decreases in the TUNEL staining suggest a potential therapeutic benefit of the CM in ameliorating PAH-mediated lung tissue damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, Korea.

ABSTRACT

Background: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may have multiple therapeutic applications for cell based therapy including the treatment of pulmonary artery hypertension (PAH). As low survival rates and potential tumorigenicity of implanted cells could undermine the mesenchymal stem cell (MSC) cell-based therapy, we chose to investigate the use of conditioned medium (CM) from a culture of MSC cells as a feasible alternative.

Methods: CM was prepared by culturing hUCB-MSCs in three-dimensional spheroids. In a rat model of PAH induced by monocrotaline, we infused CM or the control unconditioned culture media via the tail-vein of 6-week-old Sprague-Dawley rats.

Results: Compared with the control unconditioned media, CM infusion reduced the ventricular pressure, the right ventricle/(left ventricle+interventricular septum) ratio, and maintained respiratory function in the treated animals. Also, the number of interleukin 1α (IL-1α), chemokine (C-C motif) ligand 5 (CCL5), and tissue inhibitor of metalloproteinase 1 (TIMP-1)-positive cells increased in lung samples and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL)-positive cells decreased significantly in the CM treated animals.

Conclusions: From our in vivo data in the rat model, the observed decreases in the TUNEL staining suggest a potential therapeutic benefit of the CM in ameliorating PAH-mediated lung tissue damage. Increased IL-1α, CCL5, and TIMP-1 levels may play important roles in this regard.

No MeSH data available.


Related in: MedlinePlus

Localization of IL-1α, CCL5, and TIMP-1-immunoreactive cells in the lung tissues at 28 days. (A–R) Immunohistochemical expression reveals that the positive cells of IL-1α, CCL5, and TIMP-1 are significantly higher in the CM group than that in the C and M groups, and they are higher in the M group than that in the C group. (S) The increased levels of IL-1α, CCL5, and TIMP-1 immunoreactivity observed in the CM group are statistically significant. The levels of IL-1α, CCL5, and TIMP-1 immunoreactivity are significantly decreased in the CM group compared with the C and M groups. Panels A–C, G–I, and M–O are high power views of panels D–F, J–L, and P–R, respectively. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4696528&req=5

f2-jptm-2015-09-11: Localization of IL-1α, CCL5, and TIMP-1-immunoreactive cells in the lung tissues at 28 days. (A–R) Immunohistochemical expression reveals that the positive cells of IL-1α, CCL5, and TIMP-1 are significantly higher in the CM group than that in the C and M groups, and they are higher in the M group than that in the C group. (S) The increased levels of IL-1α, CCL5, and TIMP-1 immunoreactivity observed in the CM group are statistically significant. The levels of IL-1α, CCL5, and TIMP-1 immunoreactivity are significantly decreased in the CM group compared with the C and M groups. Panels A–C, G–I, and M–O are high power views of panels D–F, J–L, and P–R, respectively. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.

Mentions: Immunohistochemistry (IHC) staining of the lung tissue revealed that TIMP-1-, IL-1α-, and CCL5-positive cells were more prevalent in the CM group, and then followed by the M group in comparison with the C group at 28 days (Fig. 2A–R). These results confirmed that hUCB-MSC-CM increased the expression of certain immunomodulating cytokines (at the protein level) in the lungs of treated animals. Three weeks after hUCB-MSC-CM transfusion, TIMP-1-, IL-1α-, and CCL5-positive cells were still observed at the transplanted lung area in the CM group. The increased levels of TIMP-1, IL-1α, and CCL5 immunoreactivity observed in the M group were statistically significant (p<.05). The increased levels of CCL5 immunoreactivity were also significant in the CM group compared with the M group (Fig. 2S).


Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats.

Lee JC, Cha CI, Kim DS, Choe SY - J Pathol Transl Med (2015)

Localization of IL-1α, CCL5, and TIMP-1-immunoreactive cells in the lung tissues at 28 days. (A–R) Immunohistochemical expression reveals that the positive cells of IL-1α, CCL5, and TIMP-1 are significantly higher in the CM group than that in the C and M groups, and they are higher in the M group than that in the C group. (S) The increased levels of IL-1α, CCL5, and TIMP-1 immunoreactivity observed in the CM group are statistically significant. The levels of IL-1α, CCL5, and TIMP-1 immunoreactivity are significantly decreased in the CM group compared with the C and M groups. Panels A–C, G–I, and M–O are high power views of panels D–F, J–L, and P–R, respectively. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696528&req=5

f2-jptm-2015-09-11: Localization of IL-1α, CCL5, and TIMP-1-immunoreactive cells in the lung tissues at 28 days. (A–R) Immunohistochemical expression reveals that the positive cells of IL-1α, CCL5, and TIMP-1 are significantly higher in the CM group than that in the C and M groups, and they are higher in the M group than that in the C group. (S) The increased levels of IL-1α, CCL5, and TIMP-1 immunoreactivity observed in the CM group are statistically significant. The levels of IL-1α, CCL5, and TIMP-1 immunoreactivity are significantly decreased in the CM group compared with the C and M groups. Panels A–C, G–I, and M–O are high power views of panels D–F, J–L, and P–R, respectively. C, control; M, monocrotaline; CM, hUCB-MSCs-CM; hUCB-MSCs-CM, conditioned medium from human umbilical-cord blood derived mesenchymal cells; TIMP-1, tissue inhibitor of metalloproteinase 1; IL-1α, interleukin 1α; CCL5, chemokine (C-C motif) ligand 5. ap<.05 compared with the C group; bp<.05 compared with the M group.
Mentions: Immunohistochemistry (IHC) staining of the lung tissue revealed that TIMP-1-, IL-1α-, and CCL5-positive cells were more prevalent in the CM group, and then followed by the M group in comparison with the C group at 28 days (Fig. 2A–R). These results confirmed that hUCB-MSC-CM increased the expression of certain immunomodulating cytokines (at the protein level) in the lungs of treated animals. Three weeks after hUCB-MSC-CM transfusion, TIMP-1-, IL-1α-, and CCL5-positive cells were still observed at the transplanted lung area in the CM group. The increased levels of TIMP-1, IL-1α, and CCL5 immunoreactivity observed in the M group were statistically significant (p<.05). The increased levels of CCL5 immunoreactivity were also significant in the CM group compared with the M group (Fig. 2S).

Bottom Line: Compared with the control unconditioned media, CM infusion reduced the ventricular pressure, the right ventricle/(left ventricle+interventricular septum) ratio, and maintained respiratory function in the treated animals.Also, the number of interleukin 1α (IL-1α), chemokine (C-C motif) ligand 5 (CCL5), and tissue inhibitor of metalloproteinase 1 (TIMP-1)-positive cells increased in lung samples and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL)-positive cells decreased significantly in the CM treated animals.From our in vivo data in the rat model, the observed decreases in the TUNEL staining suggest a potential therapeutic benefit of the CM in ameliorating PAH-mediated lung tissue damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, School of Life Sciences, Chungbuk National University, Cheongju, Korea.

ABSTRACT

Background: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may have multiple therapeutic applications for cell based therapy including the treatment of pulmonary artery hypertension (PAH). As low survival rates and potential tumorigenicity of implanted cells could undermine the mesenchymal stem cell (MSC) cell-based therapy, we chose to investigate the use of conditioned medium (CM) from a culture of MSC cells as a feasible alternative.

Methods: CM was prepared by culturing hUCB-MSCs in three-dimensional spheroids. In a rat model of PAH induced by monocrotaline, we infused CM or the control unconditioned culture media via the tail-vein of 6-week-old Sprague-Dawley rats.

Results: Compared with the control unconditioned media, CM infusion reduced the ventricular pressure, the right ventricle/(left ventricle+interventricular septum) ratio, and maintained respiratory function in the treated animals. Also, the number of interleukin 1α (IL-1α), chemokine (C-C motif) ligand 5 (CCL5), and tissue inhibitor of metalloproteinase 1 (TIMP-1)-positive cells increased in lung samples and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL)-positive cells decreased significantly in the CM treated animals.

Conclusions: From our in vivo data in the rat model, the observed decreases in the TUNEL staining suggest a potential therapeutic benefit of the CM in ameliorating PAH-mediated lung tissue damage. Increased IL-1α, CCL5, and TIMP-1 levels may play important roles in this regard.

No MeSH data available.


Related in: MedlinePlus